2-174566979-C-A

Variant names:

• chr2-174566979-C-A
• rs2163236
• ENST00000409891.5:c.*65G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000409891.5(WIPF1):​c.*65G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000177 in 1,132,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: WIPF1 ENST00000409891.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330
• Publications: 6 publications found

Genes affected

WIPF1 (HGNC:12736): (WAS/WASL interacting protein family member 1) This gene encodes a protein that plays an important role in the organization of the actin cytoskeleton. The encoded protein binds to a region of Wiskott-Aldrich syndrome protein that is frequently mutated in Wiskott-Aldrich syndrome, an X-linked recessive disorder. Impairment of the interaction between these two proteins may contribute to the disease. Two transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

WIPF1 Gene-Disease associations (from GenCC):

• Wiskott-Aldrich syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• Wiskott-Aldrich syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000236449 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409891.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIPF1	NM_001375834.1	MANE Select	c.1456+91G>T		intron	N/A	NP_001362763.1	A0A140VJZ9
	WIPF1	NM_001375835.1		c.1456+91G>T		intron	N/A	NP_001362764.1	O43516-3
	WIPF1	NM_001077269.1		c.1456+91G>T		intron	N/A	NP_001070737.1	Q2YDC4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIPF1	ENST00000409891.5	TSL:1	c.*65G>T		3_prime_UTR	Exon 7 of 7	ENSP00000386431.1	O43516-2
	WIPF1	ENST00000679041.1	MANE Select	c.1456+91G>T		intron	N/A	ENSP00000503603.1	O43516-1
	WIPF1	ENST00000272746.9	TSL:1	c.1456+91G>T		intron	N/A	ENSP00000272746.5	O43516-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000177 AC: 2 AN: 1132692 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 572148

African (AFR) AF: 0.00 AC: 0 AN: 26342

American (AMR) AF: 0.00 AC: 0 AN: 35198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22292

East Asian (EAS) AF: 0.00 AC: 0 AN: 36924

South Asian (SAS) AF: 0.00 AC: 0 AN: 73646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4946

European-Non Finnish (NFE) AF: 0.00000240 AC: 2 AN: 833750

Other (OTH) AF: 0.00 AC: 0 AN: 49208

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.8
DANN	Benign	0.54
PhyloP100		-0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2163236; hg19: chr2-175431707;